title: Wnt5a signaling promotes apical and basolateral polarization of single epithelial cells.
abstract: Single epithelial-derived tumor cells have been shown to induce apical and basolateral (AB) polarity by expression of polarization-related proteins. However, physiological cues and molecular mechanisms for AB polarization of single normal epithelial cells are unclear. When intestinal epithelial cells 6 (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells formed an F-actin cap on the upper cell surface, where apical markers accumulated, and a basolateral marker was localized to the rest of the cell surface region, in a Wnt5a signaling-dependent manner. However, these phenotypes were not induced by type I collagen. Rac1 activity in the noncap region was higher than that in the cap region, whereas Rho activity increased toward the cap region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively, independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB polarization of IEC6 cells through regulation of Rac and Rho activities in a manner dependent on adhesion to specific extracellular matrix proteins.
authors.affiliation: Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Gon
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fumoto
authors.forename: Yonson
authors.initials: Y
authors.lastname: Ku
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002522:Chlorocebus aethiops; D003094:Collagen / Q000494:pharmacology; D000072261:Dishevelled Proteins; D004338:Drug Combinations; D020895:Enterocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011509:Proteoglycans / Q000494:pharmacology; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D014709:Vero Cells; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C513040:Arhgap35 protein, rat; D000072261:Dishevelled Proteins; D004338:Drug Combinations; D020662:Guanine Nucleotide Exchange Factors; D007797:Laminin; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011509:Proteoglycans; D012097:Repressor Proteins; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513259:Tiam1 protein, rat; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; C059485:matrigel; D049452:Green Fluorescent Proteins; D003094:Collagen; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins